Effects of organic salts of virucidal and antiviral compounds from Nelumbo nucifera and Kaempferia parviflora against SARS-CoV-2.

The present work investigates virucidal and antiviral compounds in the extracts of seed embryos of a lotus, Nelumbo nucifera, and a Thai ginseng, Kaempferia parviflora. Separation of the extracts led to the identification of antiviral compounds against SARS-CoV-2. Neferine (1) and nuciferine (3) from N. nucifera, as well as their respective HCl salts (2 and 4), exhibited virucidal and antiviral activities against SARS-CoV-2. Virucidal activity of neferine salt (2) (EC 4.78 µM) was 7.5 times better than its free-base, neferine (1) (EC 36.01 µM), and the salt (2) also improved the selectivity index (SI), showing less cytotoxicity than 1. This work demonstrates that organic salts have an impact on biological activities. A crude extract of K. parviflora rhizomes displayed virucidal activity (EC 42.11 µg/mL) and antiviral activity (EC 39.28 µg/mL). Isolation of a crude extract of K. parviflora rhizomes led to the identification of nine flavonoids (5-13). Among these flavonoids, only 5,7,4'-trimethoxyflavone (8) was found to show virucidal (EC 437.90 µM) and antiviral (EC 50.97 µM) activities against SARS-CoV-2. However, flavonoids (5-13) did not inhibit SARS-CoV-2 3CL enzyme at the concentrations of 10 µM and 100 µM. In conclusion, our data underscores the therapeutic potential of N. nucifera and K. parviflora derived bioactive compounds against SARS-CoV-2.